Energy balance and nutrigenetic analyses of non-Hodgkin lymphoma In the U.S, non-Hodgkin lymphoma (NHL) is the most common hematopoietic cancer in adults with >60,000 cases newly diagnosed each year. A few studies have identified some components of energy-balance: diet, exercise and obesity that are associated with NHL risk. Laboratory data show that these factors also can affect immune and inflammatory processes that may influence lymphomagenesis. Genetic susceptibility for NHL and NHL subtypes has been identified in biologically plausible pathways including immune function, inflammation, oxidative processes and in DNA repair and integrity. However, no comprehensive analyses have been conducted that integrate energy-balance factors, genetics and NHL risk. Our innovative analyses will leverage epidemiologic and genetic data already collected during in-person interviews in our large population-based case-control NHL study (2055 cases, 2081 controls) to: Aim 1) analyze diet, anthropometric and exercise data to determine associations with risk of NHL and NHL subtypes and;Aim 2) analyze gene-environment interactions to determine if single nucleotide polymorphisms (SNP) in dietary response and metabolism genes, and in inflammation and immune function genes modify the association between factors in Aim 1 and NHL risk. Unconditional logistic regression adjusted for potential confounding and effect modification will be used to obtain odds ratios as estimates of relative risk and to explore differential effects by subgroups including NHL subtypes. Energy-adjusted methods and statistical methods to assess misreporting of food frequency questionnaire (FFQ) data also will be used for analyses of nutrient data. The studys major strengths are: 1) a rich epidemiologic dataset that includes already collected exercise, anthropometrics and dietary history data collected using a validated and calibrated FFQ with frequency and portion size for specific foods, supplement use, cooking methods and macro and micronutrients computed using a relational food composition database;2) demographic and other data available to evaluate confounding and effect modification and;3) DNA already analyzed for SNPs in 146 genes in biologic pathways that may be relevant to the nutrigenetics of NHL. Results from the comprehensive analyses within our large well-defined study population will provide insight into modifiable dietary-related risk factors and nutrigenetics associated with NHL and common NHL subtypes that can help clarify the role of bioactive foods in lymphomagenesis. The information from our work also will be useful to help generate hypotheses for future research, to direct functional studies, to help identify key biologic pathways that alter susceptibility, and will be directly applicable to prevention and intervention programs to reduce NHL incidence. In addition, future pooled analyses of these and related data are planned within the InterLymph Consortium to confirm findings and to increase power and sample size for analyses by rare NHL subtypes, and for low-frequency exposures that cannot be investigated adequately in individual studies. PUBLIC HEALTH RELEVANCE: Project Narrative Incidence of non-Hodgkin lymphoma (NHL) has nearly doubled over the past 40 years and few risk factors have been established other than those associated with severe immunosuppression and some rare genetic conditions. There is growing evidence that the modifiable lifestyle factors of diet, physical activity and obesity are associated with NHL risk and that these factors act in genetic pathways that also have been associated with NHL risk. Clarifying the role that these modifiable factors play in risk of NHL and NHL subtypes will improve our understanding of NHL development, help to generate new hypotheses for future research and will be directly applicable to prevention, intervention and screening programs with a goal to reduce NHL incidence.